Effects of Recto-colic Enemas of Butyrate on the Digestive Disorders of Very Low Birth Weight Preterms <1250 Grams (NEOTRANS)

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ClinicalTrials.gov Identifier: NCT01536483

Recruitment Status
:
Terminated
(The second intermediary analysis showed no significant difference between both arms)

Clinical management of very low birth weight newborns (VLBW <1250g) consists in several challenges to adapt immature physiological systems to extrauterine life. Advances in neonatal medicine for pulmonary and/or neurological and/or cardiovascular diseases have significantly improved outcomes of these children. However, the gastro-intestinal (GI) tract remains a major cause of morbidity due to

the need of a prolonged parenteral nutrition and its complications (central venous catheter infections, sepsis, electrolyte disturbances) but without generate a high proof level on this targeted population (<1250g).

The GI functions are progressively acquired during development and are largely sensitive to the environment, especially the intestinal luminal content. Indeed, probiotics and prebiotics have shown beneficial effects upon GI functions of newborns. One of the metabolite of the gut flora potentially involved is the butyrate. Butyrate is a short chain fatty acid produced in the colon by the microbiota (carbo-hydrates degradation). The colonic amount of butyrate increases gradually after birth. The beneficial effects of butyrate are related to its properties upon the epithelial barrier (anti-inflammatory, antioxidant, barrier repair) and upon the enteric nervous system (network of neurons and glial cells) that regulate GI functions and in particular colonic motility.

To date, there is no clinical consensus to manage digestive disorders of VLBW. Several clinical studies have assessed the effects of prokinetic drugs, dietary supplements (probiotics, prebiotics) but without generate a high proof level on this targeted population. In this context, a recent study of our Research Unit (INSERM-CIC Mère-Enfant 004) has shown benefit effects of oral probiotics supplementation in children with birth weight greater than 1000g but not in extreme preterms with birth weight less than 1000g.

The main hypothesis to explain theses results lies in the intensive use of antibiotic and feeding interruption frequency in this targeted population which induce disturbances in the composition of the gut lumen (in particular the flora).

Colonic enemas assessed in various observational studies concerning VLBW seem to demonstrate a clinical efficiency upon the colonic transit, underlying by mechanical and osmotic mechanisms.

Here, the investigators propose to evaluate the clinical efficiency of butyrate enemas by a prospective randomized clinical trial blinded design.

The purpose of NEOTRANS study is to demonstrate that butyrate enemas may improve the nutritional management of extreme preterm less than 1250 grams, by facilitating the development of colic motility and clinical nutrition tolerance.

New born with a birth weight <1000g: Seven enemas of butyrate will be performed every 2 days from PND5

New born with a birth weight >1000g: Seven enemas of butyrate will be performed every day from PND5

Drug: Butyrate enemas

Seven enemas

Possibility to delay from 24 to 48 hours the procedure in case of clinical poor tolerance(maximum two enemas postponed and delayed at PND12 and PND13)

The study remains blinded for the investigation team through the intervention of a clinical research nurse

According to the procedure previously described by Nakaoka et al. (2009), a lubricated Foley catheter Ch 6 will be introduced into the rectum, the balloon will be inflated with 1 ml water for injections. Butyrate solution will be placed in a bag placed 50 cm above the child. Therefore, treatment administration will be performed at a controlled pressure of 50 cm H2O without any manual intervention

Installation time and retention is setted at 15 minutes

Treatment units will be directly placed in the incubator 30 min before the procedure to warm the enema to +36°C

Per-treatment clinical monitoring of the tolerance will be performed by a neonatologist

No Intervention: Therapeutic Abstention

The protocol will pretend enema: instillation in the diaper the product under consideration, to make the two indistinguishable processes (time, odor, wicking diaper ...)

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Ages Eligible for Study:

up to 5 Days (Child)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Any preterm infant with a birth weight less than or equal to 1250 grams admitted in the neonatal intensive care unit of Nantes Hospital